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The interface between tendon/ligament and bone tissue is a complex transition of biochemical, cellular, and mechanical properties. Investigating computational and tissue engineering models that imitate aspects of this interface may supply critical design parameters for designing future tissue replacements to promote increased biochemical and mechanical integration between tendon/ligament and bone. Strategies for modeling this tissue have typically focused on the development of heterogeneous structures to create gradients or multiphasic materials that mimic aspects of the transition. However, further work is required to elucidate the role of specific mechanical and material stimuli in recapitulating features of the tendon/ligament-bone insertion. In particular, in constructs that exhibit variation in both mechanical and biochemical properties, the interplay of mechanical, material, and chemical signals can complicate understanding of the particular factors at work in interface formation. Thus, the overall goal of this dissertation was to provide insight into the role of mechanical strain and scaffold degradability on cell behavior within heterogeneous biomaterials. Specifically, a method for determining cell vertical position within a degradable gel through a laminated interface was developed. A computational model was created to examine possible variation in local mechanical strain due to heterogeneity in mechanical properties and different interface geometries. Finally, the influence of biomaterial degradability on changes in encapsulated human mesenchymal stem cell morphology under response to cyclic mechanical strain was explored. Together, these studies provide insight into mechanical and material design considerations when devising tissue engineering strategies to regenerate the tendon/ligament-bone interface.

Blood vessels including the arteries, veins, and capillaries are a critical and indispensable component of various organisms. Some studies estimate that if all the blood vessels present in our body are arranged in line, they would amount to a total length of approximately 60,000 miles. This distance is enough to circle the world two and a half times! In addition to being all pervasive, blood vessels perform certain key functions such as delivery of oxygen and nutrients to various tissues in the body. They also assist in the spread of diseases such as cancer. Therefore, it is important to study vessels from the point of view of tissue engineering applications. In this study, I have adapted the design of an open-source 3D printed device to create channels in Poly (ethylene glycol) Maleimide (PEG-Mal) hydrogels using the subtractive technique. The PEG-Mal hydrogels can be formed in various formulations to mimic the biophysical and biochemical properties of various tissues such as bone marrow, brain, and lung. These channels created within hydrogels can be easily perfused with physiologically relevant flow rates found in blood vessels and capillaries. Additionally, I have also optimized the hydrogel formulations to improve channel reproducibility. It was found that the number of arms of PEG-Mal contributed the most to channel reproducibility with higher success rates of channel formation in 8-arm gels when compared to 4-arm gels. Therefore, this project delineates the formation of simple in vitro channels in hydrogels which combines properties of the tissue specific extracellular matrix with hemodynamics. It is expected that such a system will find potential use in various tissue engineering and disease modeling studies.